title: The Caenorhabditis elegans LET-418/Mi2 plays a conserved role in lifespan regulation.
abstract: The evolutionarily conserved nucleosome-remodeling protein Mi2 is involved in transcriptional repression during development in various model systems, plays a role in embryonic patterning and germ line development, and participates in DNA repair and cell cycle progression. It is the catalytic subunit of the nucleosome remodeling and histone deacetylase (NuRD) complex, a key determinant of differentiation in mammalian embryonic stem cells. In addition, the Drosophila and C. elegans Mi2 homologs participate in another complex, the MEC complex, which also plays an important developmental role in these organisms. Here we show a new and unexpected feature of the C. elegans Mi2 homolog, LET-418/Mi2. Lack of LET-418/Mi2 results in longevity and enhanced stress resistance, a feature that we found to be conserved in Drosophila and in Arabidopsis. The fact that depletion of other components of the NuRD and the MEC complexes did not result in longevity suggests that LET-418 may regulate lifespan in a different molecular context. Genetic interaction studies suggest that let-418 could act in the germ-cell-loss pathway, downstream of kri-1 and tcer-1. On the basis of our data and on previous findings showing a role for let-418 during development, we propose that LET-418/Mi2 could be part of a system that drives development and reproduction with concomitant life-reducing effects later in life.
authors.affiliation: Department of Biology, University of Fribourg, Fribourg, CH-1700, Switzerland.
authors.forename: Véronique
authors.initials: V
authors.lastname: De Vaux
authors.forename: Catherine
authors.initials: C
authors.lastname: Pfefferli
authors.forename: Myriam
authors.initials: M
authors.lastname: Passannante
authors.forename: Khaoula
authors.initials: K
authors.lastname: Belhaj
authors.forename: Alina
authors.initials: A
authors.lastname: von Essen
authors.forename: Simon G
authors.initials: SG
authors.lastname: Sprecher
authors.forename: Fritz
authors.initials: F
authors.lastname: Müller
authors.forename: Chantal
authors.initials: C
authors.lastname: Wicky
mesh_terms: D000818:Animals; D017360:Arabidopsis / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D004777:Environment; D019143:Evolution, Molecular; D007328:Insulin / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D018384:Oxidative Stress; D011485:Protein Binding; D020539:Sequence Analysis, Protein; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics; D015854:Up-Regulation
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; C521495:LET-418 protein, C elegans
keywords: C. elegans; FoxO transcription factor; Stress resistance; aging; germline; longevity gene